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- Title
ALOX5 promoter genotype, asthma severity and LTC<sub>4</sub> production by eosinophils.
- Authors
Kalayci, O.; Birben, E.; Sackesen, C.; Keskin, O.; Tahan, F.; Wechsler, M. E.; Civelek, E.; Soyer, O. U.; Adalioglu, G.; Tuncer, A.; Israel, E.; Lilly, C.
- Abstract
Background: The number of Sp1–Egr1 binding tandem repeats at the ALOX5 promoter influences gene transcription and may modify the response to anti-leukotriene treatment. The relationship of ALOX5 variants to asthma severity and leukotriene production by eosinophils is unknown. Objective: To characterize ALOX5 mRNA expression and cysteinyl-leukotriene production by eosinophils from individuals bearing ALOX5 promoter deletional variants and their association with the severity of childhood asthma. Methods: Eosinophils from adult asthmatics bearing only variant alleles (with other than five tandem repeats on both chromosomes, non5/non5) or no variant alleles (5/5) were cultured in vitro and ALOX5 expression and leukotriene secretion were measured. A total of 621 children with mild or moderate-severe asthma were genotyped at the ALOX5 core promoter. Results: Asthmatics with non5/non5 genotype expressed less ALOX5 mRNA and produced less LTC4 into culture supernatants than 5/5 individuals (6.4 ± 2.0 and 20.0 ± 5.0 pg/ml, n = 5; P < 0.05). More asthmatic children bearing non5/non5 genotype had moderate-severe asthma than children with the 5/5 genotype (5.3% vs. 1.4%, P = 0.008). Multivariate logistic regression identified ALOX5 promoter genotype as a significant predictor of disease severity (OR = 3.647, 95% CI: 1.146–11.608, P = 0.03). Consistent with these findings, children bearing the non5/non5 genotype had greater bronchomotor response to exercise as measured by the maximum fall after exercise and the area under the exercise curve ( P < 0.05 for both). Conclusion: Our results suggest that children who express the asthma phenotype despite having a genetic variant that impairs their ability to express ALOX5 have more severe disease and thus are more likely to have asthma symptoms.
- Publication
Allergy, 2006, Vol 61, Issue 1, p97
- ISSN
0105-4538
- Publication type
Academic Journal
- DOI
10.1111/j.1398-9995.2006.00979.x